839 results match your criteria trafficking abolished

Knockout of c-Cbl slows EGFR endocytic trafficking and enhances EGFR signaling despite incompletely blocking receptor ubiquitylation.

Pharmacol Res Perspect 2021 Apr;9(2):e00756

Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.

Epidermal growth factor receptor (EGFR) activity is necessary and sufficient for corneal epithelial homeostasis. However, the addition of exogenous Epidermal Growth Factor (EGF) does not reliably restore the corneal epithelium when wounded. This is likely due to high levels of endogenous EGF in tear fluid as well as desensitization of the EGFR following ligand stimulation. Read More

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EDS1-interacting J protein 1 is an essential negative regulator of plant innate immunity in Arabidopsis.

Plant Cell 2021 Mar;33(1):153-171

Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement & Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China.

Plants have evolved precise mechanisms to optimize immune responses against pathogens. ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) plays a vital role in plant innate immunity by regulating basal resistance and effector-triggered immunity. Nucleocytoplasmic trafficking of EDS1 is required for resistance reinforcement, but the molecular mechanism remains elusive. Read More

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Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia.

Sci Rep 2021 Mar 4;11(1):5127. Epub 2021 Mar 4.

Department of Haematology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450000, China.

The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. Read More

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Dietary Geranylgeranyl Pyrophosphate Counteracts the Benefits of Statin Therapy in Experimental Pulmonary Hypertension.

Circulation 2021 Mar 4. Epub 2021 Mar 4.

Department of Pathophysiology, School of Basic Medicine; Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown. Read More

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Profilin promotes formin-mediated actin filament assembly and vesicle transport during polarity formation in pollen.

Plant Cell 2021 Feb 8. Epub 2021 Feb 8.

Center for Biological Science and Technology, Institute of Natural Science, Beijing Normal University, Zhuhai 519087, China.

Pollen germination is critical for the reproduction of flowering plants. Formin-dependent actin polymerization plays vital roles in vesicle trafficking and polarity establishment during this process. However, how formin-mediated actin assembly is regulated in vivo remains poorly understood. Read More

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February 2021

Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor.

Sci Rep 2021 Feb 25;11(1):4537. Epub 2021 Feb 25.

Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70125, Bari, Italy.

Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. Several disorders, including hypertension and inappropriate antidiuretic hormone secretion (SIADH), are associated with abnormalities in water homeostasis. It has been shown that certain phytocompounds are beneficial to human health. Read More

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February 2021

Induced Arp2/3 Complex Depletion Increases FMNL2/3 Formin Expression and Filopodia Formation.

Front Cell Dev Biol 2021 1;9:634708. Epub 2021 Feb 1.

Zoological Institute, Technische Universität Braunschweig, Braunschweig, Germany.

The Arp2/3 complex generates branched actin filament networks operating in cell edge protrusion and vesicle trafficking. Here we employ a conditional knockout mouse model permitting tissue- or cell-type specific deletion of the murine gene (encoding Arp3). A functional gene appeared essential for fibroblast viability and growth. Read More

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February 2021

K1.5-Kβ1.3 Recycling Is PKC-Dependent.

Int J Mol Sci 2021 Jan 29;22(3). Epub 2021 Jan 29.

Instituto de Investigaciones Biomédicas Madrid CSIC-UAM. C/Arturo Duperier 4, 28029 Madrid, Spain.

K1.5 channel function is modified by different regulatory subunits. Kβ1. Read More

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January 2021

β-Adrenergic control of sarcolemmal Ca1.2 abundance by small GTPase Rab proteins.

Proc Natl Acad Sci U S A 2021 Feb;118(7)

Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA 95616;

The number and activity of Ca1.2 channels in the cardiomyocyte sarcolemma tunes the magnitude of Ca-induced Ca release and myocardial contraction. β-Adrenergic receptor () activation stimulates sarcolemmal insertion of Ca1. Read More

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February 2021

Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps.

Viruses 2021 02 2;13(2). Epub 2021 Feb 2.

Department of Cell and Molecular Biology, School of Medicine of Ribeirao Preto, University of Sao Paulo, São Paulo 14049-900, Brazil.

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract, and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Read More

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February 2021

DPP4 Inhibitor Sitagliptin Enhances Lymphocyte Recruitment and Prolongs Survival in a Syngeneic Ovarian Cancer Mouse Model.

Cancers (Basel) 2021 Jan 27;13(3). Epub 2021 Jan 27.

Centre for Cancer Research, Hudson Institute of Medical Research, Clayton 3168, Australia.

Immunity plays a key role in epithelial ovarian cancer (EOC) progression with a well-documented correlation between patient survival and high intratumoral CD8+ to T regulatory cell (Treg) ratios. We previously identified dysregulated DPP4 activity in EOCs as a potentially immune-disruptive influence contributing to a reduction in CXCR3-mediated T-cell infiltration in solid tumours. We therefore hypothesized that inhibition of DPP4 activity by sitagliptin, an FDA-approved inhibitor, would improve T-cell infiltration and function in a syngeneic ID8 mouse model of EOC. Read More

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January 2021

Autophagy Blockade Limits HER2+ Breast Cancer Tumorigenesis by Perturbing HER2 Trafficking and Promoting Release Via Small Extracellular Vesicles.

Dev Cell 2021 Feb 19;56(3):341-355.e5. Epub 2021 Jan 19.

Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Electronic address:

Autophagy modulation is an emerging strategy for cancer therapy. By deleting an essential autophagy gene or disrupting its autophagy function, we determined a mechanism of HER2+ breast cancer tumorigenesis by directly regulating the oncogenic driver. Disruption of FIP200-mediated autophagy reduced HER2 expression on the tumor cell surface and abolished mammary tumorigenesis in MMTV-Neu mice. Read More

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February 2021

Difference of pain vulnerability in adult and juvenile rodents: the role of SIRT1-mediated ClC-3 trafficking in sensory neurons.

Pain 2021 Jan 5. Epub 2021 Jan 5.

Medical Research Center of Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Rd. 2, Guangzhou 510080, China Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Rd. 2, Guangzhou 510080, China Zhongshan School of Medicine of Sun Yat-sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China College of Food Science and Technology, Hainan University, 58 Renmin Avenue, Haikou 570228, China State Key Laboratory of Marine Resources Utilization of South China Sea, 58 Renmin Avenue, Haikou 570228, China.

Abstract: Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 as important aging-related protein with function of lifespan extension, whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. Read More

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January 2021

Protein disulfide isomerase-mediated S-nitrosylation facilitates surface expression of P2X7 receptor following status epilepticus.

J Neuroinflammation 2021 Jan 6;18(1):14. Epub 2021 Jan 6.

Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University, Kangwon-Do, Chuncheon, 24252, South Korea.

Background: P2X7 receptor (P2X7R) is an ATP-gated nonselective cationic channel playing important roles in a variety of physiological functions, including inflammation, and apoptotic or necrotic cell death. An extracellular domain has ten cysteine residues forming five intrasubunit disulfide bonds, which are needed for the P2X7R trafficking to the cell surface and the recognition of surface epitopes of apoptotic cells and bacteria. However, the underlying mechanisms of redox/S-nitrosylation of cysteine residues on P2X7R and its role in P2X7R-mediated post-status epilepticus (SE, a prolonged seizure activity) events remain to be answered. Read More

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January 2021

Suppression of liver transplant rejection by anti-donor MHC antibodies via□ depletion of donor immunogenic dendritic cells.

Int Immunol 2020 Dec 1. Epub 2020 Dec 1.

Dept. Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan.

Background: We previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC antigen (DST-antibodies).

Methods: We examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model. Read More

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December 2020

Axon Injury-Induced Autophagy Activation Is Impaired in a Model of Tauopathy.

Int J Mol Sci 2020 Nov 13;21(22). Epub 2020 Nov 13.

Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

Autophagy is a conserved pathway that plays a key role in cell homeostasis in normal settings, as well as abnormal and stress conditions. Autophagy dysfunction is found in various neurodegenerative diseases, although it remains unclear whether autophagy impairment is a contributor or consequence of neurodegeneration. Axonal injury is an acute neuronal stress that triggers autophagic responses in an age-dependent manner. Read More

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November 2020

Nuclear partitioning of Prohibitin 1 inhibits Wnt/β-catenin-dependent intestinal tumorigenesis.

Oncogene 2021 01 3;40(2):369-383. Epub 2020 Nov 3.

Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado, Aurora, CO, USA.

The Wnt/β-catenin signaling pathway is aberrantly activated in the majority of colorectal cancer cases due to somatic mutations in the adenomatous polyposis coli (APC) gene. Prohibitin 1 (PHB1) serves pleiotropic cellular functions with dynamic subcellular trafficking, facilitating signaling crosstalk between organelles. Nuclear-localized PHB1 is an important regulator of gene transcription. Read More

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January 2021

A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export.

Nat Commun 2020 11 3;11(1):5559. Epub 2020 Nov 3.

Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK.

Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, we perform a genome-wide CRISPR screen using an endogenous cholesterol reporter and identify >100 genes involved in LDL-cholesterol import. We characterise C18orf8 as a core subunit of the mammalian Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required for complex stability and function. Read More

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November 2020

ER-to-Golgi Transport in HeLa Cells Displays High Resilience to Ca and Energy Stresses.

Cells 2020 10 17;9(10). Epub 2020 Oct 17.

Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria.

One third of all human proteins are either transmembrane or soluble secretory proteins that first target the endoplasmic reticulum (ER). These proteins subsequently leave the ER and enter the Golgi apparatus via ER-Golgi intermediate vesicular structures. Live-cell imaging of cargos fused to fluorescent proteins (FPs) enables the high-resolution visualization and characterization of secretory transport processes. Read More

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October 2020

Pathomechanisms of a Mutation Found in a Russian Family Suffering From Becker's Myotonia.

Front Neurol 2020 4;11:1019. Epub 2020 Sep 4.

Section of Pharmacology, Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari Aldo Moro, Bari, Italy.

Myotonia congenita (MC) is a rare muscle disease characterized by sarcolemma over-excitability inducing skeletal muscle stiffness. It can be inherited either as an autosomal dominant (Thomsen's disease) or an autosomal recessive (Becker's disease) trait. Both types are caused by loss-of-function mutations in the gene, encoding for ClC-1 chloride channel. Read More

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September 2020

Wnt5b/Ryk-mediated membrane trafficking of P2X3 receptors contributes to bone cancer pain.

Exp Neurol 2020 12 24;334:113482. Epub 2020 Sep 24.

Department of Pharmacology, School of Pharmacy, Henan University, Kaifeng, Henan, China. Electronic address:

Wnt5b, a member of Wnt family, plays multiple roles in tumor progression and metastasis. However, whether Wnt5b contributes to the sensitization of dorsal root ganglia (DRG) neurons and pathogenesis of bone cancer pain still remains unclear. Here, we found that the protein expression of Wnt5b and its atypical tyrosine protein kinase receptor Ryk was upregulated in ipsilateral DRGs in tumor-bearing mice. Read More

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December 2020

The interplays between Crimean-Congo hemorrhagic fever virus (CCHFV) M segment-encoded accessory proteins and structural proteins promote virus assembly and infectivity.

PLoS Pathog 2020 09 21;16(9):e1008850. Epub 2020 Sep 21.

CIRI-Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, 46 allée d'Italie, Lyon, France.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne orthonairovirus that has become a serious threat to the public health. CCHFV has a single-stranded, tripartite RNA genome composed of L, M, and S segments. Cleavage of the M polyprotein precursor generates the two envelope glycoproteins (GPs) as well as three secreted nonstructural proteins GP38 and GP85 or GP160, representing GP38 only or GP38 linked to a mucin-like protein (MLD), and a double-membrane-spanning protein called NSm. Read More

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September 2020

Ghrelin system is involved in improvements in glucose metabolism mediated by hyperbaric oxygen treatment in a streptozotocin‑induced type 1 diabetes mouse model.

Mol Med Rep 2020 Nov 2;22(5):3767-3776. Epub 2020 Sep 2.

Department of Special Medicine, Medical College, Qingdao University, Qingdao, Shandong 266071, P.R. China.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder for which the only effective therapy is insulin replacement. Hyperbaric oxygen (HBO) therapy has demonstrated potential in improving hyperglycemia and as a treatment option for T1DM. Ghrelin and HBO have been previously reported to exert proliferative, anti‑apoptotic and anti‑inflammatory effects in pancreatic cells. Read More

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November 2020

Ezetimibe impairs transcellular lipid trafficking and induces large lipid droplet formation in intestinal absorptive epithelial cells.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 12 27;1865(12):158808. Epub 2020 Aug 27.

Department of Biochemistry, Faculty of Medicine, Saitama Medical University, Saitama, Japan.

Ezetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1) protein, which mediates intracellular cholesterol trafficking from the brush border membrane to the endoplasmic reticulum, where chylomicron assembly takes place in enterocytes or in the intestinal absorptive epithelial cells. Cholesterol is a minor lipid constituent of chylomicrons; however, whether or not a shortage of cholesterol attenuates chylomicron assembly is unknown. The aim of this study was to examine the effect of ezetimibe, a potent NPC1L1 inhibitor, on trans-epithelial lipid transport, and chylomicron assembly and secretion in enterocytes. Read More

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December 2020

Reelin depletion protects against autoimmune encephalomyelitis by decreasing vascular adhesion of leukocytes.

Sci Transl Med 2020 08;12(556)

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Neuroinflammation as a result of immune cell recruitment into the central nervous system (CNS) is a key pathogenic mechanism of multiple sclerosis (MS). However, current anti-inflammatory interventions depleting immune cells or directly targeting their trafficking into the CNS can have serious side effects, highlighting a need for better immunomodulatory strategies. We detected increased Reelin concentrations in the serum of patients with MS, resulting in increased endothelial permeability to leukocytes through increased nuclear factor κB-mediated expression of vascular adhesion molecules. Read More

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PTEN Is Required for The Anti-Epileptic Effects of AMPA Receptor Antagonists in Chronic Epileptic Rats.

Int J Mol Sci 2020 Aug 6;21(16). Epub 2020 Aug 6.

Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, Korea.

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is one of the ligand-gated ion channels for glutamate, which is an important player in the generation and spread of seizures. The efficacy of AMPAR functionality is regulated by the trafficking, synaptic targeting, and phosphorylation. Paradoxically, AMPAR expression and its phosphorylation level are decreased in the epileptic hippocampus. Read More

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Arabidopsis COPPER TRANSPORTER 1 undergoes degradation in a proteasome-dependent manner.

J Exp Bot 2020 10;71(19):6174-6186

Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China.

The essential nutrient copper is toxic in excess. Therefore, plants must tightly control copper uptake and distribution. Arabidopsis thaliana high-affinity copper transporters (COPTs) mediate copper uptake, partitioning, and redistribution. Read More

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October 2020

Imaging niacin trafficking with positron emission tomography reveals in vivo monocarboxylate transporter distribution.

Nucl Med Biol 2020 Jul 6;88-89:24-33. Epub 2020 Jul 6.

School of Biomedical Engineering & Imaging Sciences, King's College London, St Thomas' Hospital, London SE1 7EH, United Kingdom. Electronic address:

Introduction: A sufficient dietary intake of the vitamin niacin is essential for normal cellular function. Niacin is transported into the cells by the monocarboxylate transporters: sodium-dependent monocarboxylate transporter (SMCT1 and SMCT2) and monocarboxylate transporter (MCT1). Despite the importance of niacin in biological systems, surprisingly, its in vivo biodistribution and trafficking in living organisms has not been reported. Read More

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Transcytosis via the late endocytic pathway as a cell morphogenetic mechanism.

EMBO J 2020 08 13;39(16):e105332. Epub 2020 Jul 13.

Directors' Research Unit, European Molecular Biology Laboratory, Heidelberg, Germany.

Plasma membranes fulfil many physiological functions. In polarized cells, different membrane compartments take on specialized roles, each being allocated correct amounts of membrane. The Drosophila tracheal system, an established tubulogenesis model, contains branched terminal cells with subcellular tubes formed by apical plasma membrane invagination. Read More

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Multiple basic amino acid residues contribute to phosphatidic acid-mediated inhibition of rice potassium channel OsAKT2.

Plant Signal Behav 2020 09 10;15(9):1789818. Epub 2020 Jul 10.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Life Sciences, Nanjing Agricultural University , Nanjing, China.

Anionic phospholipid phosphatidic acid (PA) behaves as an important second messenger involved in many cellular processes, such as development, cytoskeletal dynamics, vesicle trafficking, and stress response. Recently, it was reported that PA can directly bind with the rice Shaker K channel OsAKT2 to inhibit its channel activity. Two adjacent arginine residues (R644 and R645) in ANK domain were identified as a PA-binding site essential to the PA-mediated inhibition of OsAKT2. Read More

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September 2020